Brain catecholamines and serotonin have been shown to be involved in central nervous system regulation of blood pressure. In particular, hypothalamic and brainstem nuclei containing high concentrations of these neurotransmitters form an axis of blood pressure regulatory neurons. Clinically important antihypertensive agents such as alphamethyldopa and clonidine reduce sympathetic outflow from the brain by inhibiting central catecholamine neurons. While noradrenergic neurons have been most implicated in the mechanism of action of central acting antihypertensive drugs, serotonergic neurons also play a role in blood pressure regulation. We have shown that chronic infusions of the serotonin precursor 5-hydroxytryptophan increase brain serotonin turnover and reduce blood pressure in normotensive rats. We have now adapted in vivo electrochemical techniques to make it possible to study nonrepinephrine and serotonin release continuously from specific nuclei in brain of awake rats. Preliminary experiments have shown that intravenous phenylephrine infusions which increase blood pressure cause an increase in Serotonin release in dorsal raphe nucleus. Norepinephrine release initially falls but then subsequently increases. These results are compatible with the hypothesis that the brain compensates for hypertension by reducing sympathetic outflow through increased central serotonergic tone and reduced noradrenergic tone. We plan to use in vivo electrochemistry to study noradrenergic and serotonergic neuronal responses to acute and chronic hypertension and hypotension. Awake rats from both normotensive and hypertensive strains will be studied. Hypertension will be produced with infusions of vasopressors such as phenylephrine and hypotension will be induced by vasodilators such as hydralazine and beta blockers such as propranolol. In addition, central acting antihypertensive drugs such as clonidine will be evaluated. Regions to be studied include hypothalamus, locus coeruleus, nucleus tractus solitarius and dorsal raphe nucleus. These experiments should help clarify the interactive role of norepinephrine and serotonin in blood pressure regulation and indicate the relative importance of each neurotransmitter in individual vasoregulatory nuclei.